POS0263 RE-VACCINATION COMPARED TO BOOSTER COVID-19 mRNA VACCINATION SIGNIFICANTLY INCREASES THE SEROLOGICAL RESPONSE IN RITUXIMAB-TREATED PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASES WITHOUT A PRIMARY DETECTABLE SEROLOGICAL COVID-19 VACCINE RESPONSE
Authors: C. Ammitzbøll, M. K. Thomsen, M. L. F. Hermansen, S. R. Vils, J. B. Andersen, A. D. Johannesen, F. Szabados, C. M. Jørgensen, M. C. L. Larsen, C. Erikstrup, E. M. Hauge, A. Troldborg
Journal: Annals of the Rheumatic Diseases (2022)

Background Reports of an impaired humoral response after COVID-19 vaccination in patients treated with rituximab (RTX) have raised particular concern for patients with inflammatory rheumatic diseases (IRD) receiving RTX (1). This calls for strategies to enhance a humoral response in RTX-treated patients. At present, there is no data on whether it is best to increase the humoral response with a third vaccine dose (a booster) or with a third and fourth dose (re-vaccination). Objectives In IRD patients treated with RTX, without a detectable humoral response after the first vaccination course (two shots), we aimed to investigate the difference of either a booster vaccine (dose 3) or a new re-vaccination course (dose 3 + 4) on the serological response of the COVID-19 mRNA vaccines. Methods We included 84 patients with IRD treated with RTX, all without measurable total SARS-CoV-2 antibodies after a full primary COVID-19 vaccination course (2 doses three weeks apart). All patients were offered a new re-vaccination course with the mRNA vaccine not used primarily (Pfizer/Biontec or Moderna). A small number of patients declined the revaccination, and recieved a booster with the mRNA vaccine used initially. Serum total antibodies were measured before and six weeks after the last dose against recombinant SARS-CoV-2 spike S1 protein (VITROS). In addition, CD19+ B-cells were measured at inclussion. Results Patient characteristics are in Table 1. The median age was 64 years; 68% were female with a disease duration of 5 years. Sixty-nine out of 84 were re-vaccinated (3 + 4 dose). Details previous exposure to RTX are given in Table 1. CD19+ B-cells were measurable in 12/81 at inclusion. Table 1. Patient Characteristics Booster, n=15 Revaccination, n=69 Age, years median (IQR) 60 (45 - 69) 65 (54 - 70) Female 47% 72% Disease duration, years (IQR) 5 (2-8) 6(2 - 13) ANCA-vasculitis 47 % 45 % Rheumatoid Arthritis 47 % 17 % Poly- Dermatomyositis 6 % 19 % SLE, Scleroderma, other diagnoses - 19 % No DMARD treatment 27 % 35 % Prednisone 33 % 46 % Methotrexate 40 % 16 % Azathioprine 7 % 12 % Mycophenolate 7 % 7 % Other 20 % 9 % Rituximab treatment, (IQR ) Months from last RTX to vaccination 3.9 (1.3 - 9.3) 5.4 (4.2 - 7.3) Number of infusions 6 (4 - 8) 7 (5 - 12) Cummulativ total dose, gram 4 (2.5 - 7.5) 6 (3.5 - 10) Total treatment time with RTX, months 15 (9 - 54) 27 (13 - 63) Patients with measurable CD19+ B-cells in peripheral blood at the time of booster or re-vaccination (positive/total) 3/14 9/67 We found a combined seroconversion rate of 33% six weeks after the last shot. There was no statistical difference between the booster (38,5%) and the re-vaccination group (32,3%), p=0.67 (Pearson’s chi-squared). IRD patients with a humoral response in the re-vaccination group had significantly higher levels of total SARS-CoV-2 antibodies (median(IQR) 306(49-464) AU/ml) compared to the booster group (14(4-15) AU/ml) p=0.02, Figure 1A. In multiple logistic regression model, we found that levels of CD19+ B-cells were the only variable able to predict a humoral response, Figure 1B. However, only 39% of the patients with a humoral response to vaccination had measurable CD19+ B-cells before vaccination. We found no effect of age, sex, diagnosis, treatment, and RTX exposure on the chance of seroconversion in multiple logistic regression models when corrected for CD19+ B-cells. Figure 1. Conclusion We found that re-vaccination (dose 3 + 4) with COVID-19 mRNA vaccines favored a high humoral response in patients with IRD treated with RTX, who did not have a detectable humoral response after the first two vaccine doses, compared to a booster shot (dose 3). A detectable humoral response after re-vaccination was seen in more than half of the patients with no measurable CD19+ B-cells before vaccination. Presence of circulating CD19+ B-cells are a significant predictor of humoral response to mRNA COVID-19 vaccination. References [1]Ammitzbøll et al. ACR Open Rheum. 2021 Sep;3(9):622-628. doi: 10.1002/acr2.11299. Acknowledgements The Danish Rheumatism Association - Gigtforeningen for funding the study. Disclosure of Interests None declared